We are studying and comparing the prophylactic therapeutic effects of lithium with carbamazepine in a double-blind, randomized, crossover design followed by a period of treatment with both drugs in combination, in outpatients with manic-depressive illness. We intend to further explore the possible differential clinical efficacy of lithium, carbamazepine, and the combination, and assess possible clinical and biological correlates of response. We now have 36 patients (27 of whom have entered the randomized drug trial) and plan to recruit a total of 50 patients. Each patient will have the following tests: blood count, thyroid functions, SMAC, 24-hour urine collection for urinary free cortisol and neurotransmitter metabolites, TRH stimulation, DST, lumbar puncture, EEG, MRI, EKG, and an extensive battery of neuropsychological tests. Patients have an extensive history taken, a life chart constructed, and psychosensory symptoms assessed. A number of self- and observer-ratings are performed. This study is too early in its course (each patient will be studied for three years and the study began in October 1988) to report any results.